Poliovirus receptor (CD155) and Nectin-2 (CD112) (CD155/CD112)

DNAM-1 ligands, primarily Poliovirus receptor (CD155) and Nectin-2 (CD112), are cell surface glycoproteins belonging to the immunoglobulin superfamily that play a critical role in modulating immune responses against tumor cells [UniProt: P15151, Q92692]. These ligands are frequently overexpressed on various malignancies, including melanoma, lung cancer, and colorectal cancer, where they interact with a network of receptors on Natural Killer (NK) cells and T cells [PubMed: 29379211]. The primary activating receptor for these ligands is DNAM-1 (CD226), which triggers tumor cell lysis and cytokine production upon binding. However, these ligands also bind with higher affinity to inhibitory receptors such as TIGIT, CD96, and PVRIG, leading to immune evasion and T-cell exhaustion in the tumor microenvironment [PubMed: 33033268]. Therapeutic strategies targeting this axis focus on blocking the inhibitory interactions—most notably through anti-TIGIT and anti-PVRIG antibodies—to restore DNAM-1-mediated anti-tumor immunity. Clinical development is currently centered on monoclonal antibodies that disrupt the TIGIT/CD155 and PVRIG/CD112 pathways to enhance the efficacy of existing checkpoint inhibitors [ClinicalTrials.gov].

Other names

PVRCD155Necl-5Tage4Nectin-2CD112PVRL2HVEBDNAM-1 ligands

Blocking the interaction between tumor-expressed ligands (CD155/CD112) and inhibitory receptors (TIGIT, PVRIG, CD96) on immune cells to promote DNAM-1-mediated activation [PubMed: 33033268].